scholarly journals pH-Sensitive Biomaterials for Drug Delivery

Molecules ◽  
2020 ◽  
Vol 25 (23) ◽  
pp. 5649
Author(s):  
Shijie Zhuo ◽  
Feng Zhang ◽  
Junyu Yu ◽  
Xican Zhang ◽  
Guangbao Yang ◽  
...  
Keyword(s):  
Drug Delivery ◽  
Medical Application ◽  
Ph Sensitive ◽  
Great Promise ◽  
Responsive Materials ◽  
And Personalized Medicine ◽  
Microenvironment Ph ◽  
Pathological Tissues

The development of precise and personalized medicine requires novel formulation strategies to deliver the therapeutic payloads to the pathological tissues, producing enhanced therapeutic outcome and reduced side effects. As many diseased tissues are feathered with acidic characteristics microenvironment, pH-sensitive biomaterials for drug delivery present great promise for the purpose, which could protect the therapeutic payloads from metabolism and degradation during in vivo circulation and exhibit responsive release of the therapeutics triggered by the acidic pathological tissues, especially for cancer treatment. In the past decades, many methodologies, such as acidic cleavage linkage, have been applied for fabrication of pH-responsive materials for both in vitro and in vivo applications. In this review, we will summarize some pH-sensitive drug delivery system for medical application, mainly focusing on the pH-sensitive linkage bonds and pH-sensitive biomaterials.

scholarly journals The TAT Protein Transduction Domain as an Intra-Articular Drug Delivery Technology

Cartilage ◽  
2020 ◽  
pp. 194760352095939
Author(s):  
Sarah E. Mailhiot ◽  
Matthew A. Thompson ◽  
Akiko E. Eguchi ◽  
Sabrina E. Dinkel ◽  
Martin K. Lotz ◽  
...  
Keyword(s):  
Drug Delivery ◽  
Genetic Recombination ◽  
Great Promise ◽  
Tat Protein ◽  
Binding Studies ◽  
Osteoarthritic Cartilage ◽  
Peptide Transduction ◽  
Delivery Technology

Objective Intra-articular drug delivery holds great promise for the treatment of joint diseases such as osteoarthritis. The objective of this study was to evaluate the TAT peptide transduction domain (TAT-PTD) as a potential intra-articular drug delivery technology for synovial joints. Design Experiments examined the ability of TAT conjugates to associate with primary chondrocytes and alter cellular function both in vitro and in vivo. Further experiments examined the ability of the TAT-PTD to bind to human osteoarthritic cartilage. Results The results show that the TAT-PTD associates with chondrocytes, is capable of delivering siRNA for chondrocyte gene knockdown, and that the recombinant enzyme TAT-Cre is capable of inducing in vivo genetic recombination within the knee joint in a reporter mouse model. Last, binding studies show that osteoarthritic cartilage preferentially uptakes the TAT-PTD from solution. Conclusions The results suggest that the TAT-PTD is a promising delivery strategy for intra-articular therapeutics.

In vitro and in vivo chemo-phototherapy of magnetic TiO2 drug delivery system formed by pH-sensitive coordination bond

2016 ◽  
Vol 31 (4) ◽  
pp. 568-581 ◽  
Author(s):  
Huijuan Zhang ◽  
Yandan Ji ◽  
Qianqian Chen ◽  
Xing Zhu ◽  
Xiaoge Zhang ◽  
...  
Keyword(s):  
Drug Delivery ◽  
Drug Delivery System ◽  
Delivery System ◽  
Ph Sensitive ◽  
Coordination Bond

Hybrid bicelles as a pH-sensitive nanocarrier for hydrophobic drug delivery

RSC Advances ◽  
2016 ◽  
Vol 6 (83) ◽  
pp. 79811-79821 ◽  
Author(s):  
Li Lin ◽  
Xiaoyou Wang ◽  
Yanyu Guo ◽  
Kuan Ren ◽  
Xiaoda Li ◽  
...  
Keyword(s):  
Drug Delivery ◽  
Therapeutic Effect ◽  
Cellular Uptake ◽  
Ph Sensitive ◽  
Hydrophobic Drug ◽  
Tumor Accumulation

Stabilized disc-like hybrid bicelles provide pH-sensitive release, preferable cellular uptake, tumor accumulation and therapeutic effect in vitro and in vivo.

scholarly journals Development of Targetable Multi-Drug Nanoparticles for Glioblastoma Treatment and In Vitro Evaluation in Glioblastoma Stem Cells

2020 ◽  
Author(s):  
Shelby B. Smiley ◽  
Yeonhee Yun ◽  
Pranav Ayyagari ◽  
Harlan E. Shannon ◽  
Karen E. Pollok ◽  
...  
Keyword(s):  
Drug Delivery ◽  
Stem Cells ◽  
Therapeutic Option ◽  
Double Emulsion ◽  
Standard Of Care ◽  
Great Promise ◽  
In Vivo Models ◽  
Drug Nanoparticles

AbstractGlioblastoma (GBM) is a malignant brain tumor with a poor long-term prognosis. The current median survival is approximately fifteen to twenty months with the standard of care therapy which includes surgery, radiation, and chemotherapy. An important factor contributing to recurrence of GBM is high resistance of GBM cancer stem cells (CSCs) to several anticancer drugs, for which a systemically delivered single drug approach will be unlikely to produce a viable cure. Therefore, multidrug therapies have the potential to improve the survival time. Currently, only temozolomide (TMZ), which is a DNA alkylator, affects overall survival in GBM patients. CSCs regenerate rapidly and over-express a methyl transferase which overrides the DNA-alkylating mechanism of TMZ, leading to drug resistance. Idasanutlin (RG7388, R05503781) is a potent, selective MDM2 antagonist that additively kills GBM CSCs when combined with TMZ. Nanotechnology is an emerging field that shows great promise in drug delivery and diagnostics. The ability to combine both therapy and imaging allows real time assessment of drug delivery in vivo for the field of theranostics.To develop a multi-drug therapy using multi-functional nanoparticles (NPs) that preferentially target the GBM CSC subpopulation and provide in vivo preclinical imaging capability. Polymer-micellar NPs composed of poly(styrene-b-ethylene oxide) (PS-b-PEO) and poly(lactic-co-glycolic) acid (PLGA) were developed investigating both single and double emulsion fabrication techniques as well as combinations of TMZ and RG7388. The NPs were covalently bound to a 15-base-pair CD133 aptamer in order to target the CD133 antigen expressed on the surface of GBM CSC subpopulation. For theranostic functionality, the NPs were also labelled with a radiotracer, Zirconium-89 (89Zr). The NPs maintained a small size of less than 100 nm, a low negative charge and exhibited the ability to effectively target and kill the CSC subpopulation. In addition, the conjugation of the CD133 aptamer was able to promote killing in CSCs leading to the justification of a targeted nanosystem to potentially improve localized therapy in future in vivo models. This work has provided a potentially therapeutic option for GBM specific for CSC targeting and theranostic imaging.

scholarly journals The TAT Protein Transduction Domain as an Intra-articular Drug-Delivery Technology

2020 ◽  
Author(s):  
Sarah E. Mailhiot ◽  
Matthew A. Thompson ◽  
Akiko E. Eguchi ◽  
Sabrina E. Dinkel ◽  
Martin K. Lotz ◽  
...  
Keyword(s):  
Drug Delivery ◽  
Genetic Recombination ◽  
Great Promise ◽  
Tat Protein ◽  
Binding Studies ◽  
Osteoarthritic Cartilage ◽  
Peptide Transduction ◽  
Delivery Technology

AbstractObjectiveIntra-articular drug delivery holds great promise for the treatment of joint diseases such as osteoarthritis. The objective of this study was to evaluate the TAT peptide transduction domain (TAT-PTD) as a potential intra-articular drug delivery technology for synovial joints.DesignExperiments examined the ability of TAT conjugates to associate with primary chondrocytes and alter cellular function both in vitro and in vivo. Further experiments examined the ability of the TAT-PTD to bind to human osteoarthritic cartilage.ResultsThe results show that the TAT-PTD associates with chondrocytes, is capable of delivering siRNA for chondrocyte gene knockdown, and that the recombinant enzyme TAT-Cre is capable of inducing in vivo genetic recombination within the knee joint in a reporter mouse model. Lastly, binding studies show that osteoarthritic cartilage preferentially uptakes the TAT-PTD from solution.ConclusionsThe results suggest that the TAT-PTD is a promising delivery strategy for intra-articular therapeutics.

Supermolecular theranostic capsules for pH-sensitive magnetic resonance imaging and multi-responsive drug delivery

2015 ◽  
Vol 3 (43) ◽  
pp. 8499-8507 ◽  
Author(s):  
Di-Wei Zheng ◽  
Qi Lei ◽  
Si Chen ◽  
Wen-Xiu Qiu ◽  
Meng-Yi Liu ◽  
...  
Keyword(s):  
Magnetic Resonance Imaging ◽  
Drug Delivery ◽  
Magnetic Resonance ◽  
Ph Sensitive ◽  
Layer By Layer ◽  
Resonance Imaging ◽  
Macromolecular Drug Delivery ◽  
Macromolecular Drug

Novel layer by layer (LBL) microcapsules for macromolecular drug delivery and pH-sensitive MR imaging were designed and tested both in vitro and in vivo.

Recent In Vitro and In Silico Advances in the Understanding of Intranasal Drug Delivery

2020 ◽  
Vol 26 ◽  
Author(s):  
John Chen ◽  
Andrew Martin ◽  
Warren H. Finlay
Keyword(s):  
Drug Delivery ◽  
In Silico ◽  
Local Drug Delivery ◽  
In Vivo Studies ◽  
Intranasal Drug Delivery ◽  
Nasal Sprays ◽  
In Silico Studies ◽  
Drug Delivery Devices

Background: Many drugs are delivered intranasally for local or systemic effect, typically in the form of droplets or aerosols. Because of the high cost of in vivo studies, drug developers and researchers often turn to in vitro or in silico testing when first evaluating the behavior and properties of intranasal drug delivery devices and formulations. Recent advances in manufacturing and computer technologies have allowed for increasingly realistic and sophisticated in vitro and in silico reconstructions of the human nasal airways. Objective: To perform a summary of advances in understanding of intranasal drug delivery based on recent in vitro and in silico studies. Conclusion: The turbinates are a common target for local drug delivery applications, and while nasal sprays are able to reach this region, there is currently no broad consensus across the in vitro and in silico literature concerning optimal parameters for device design, formulation properties and patient technique which would maximize turbinate deposition. Nebulizers are able to more easily target the turbinates, but come with the disadvantage of significant lung deposition. Targeting of the olfactory region of the nasal cavity has been explored for potential treatment of central nervous system conditions. Conventional intranasal devices, such as nasal sprays and nebulizers, deliver very little dose to the olfactory region. Recent progress in our understanding of intranasal delivery will be useful in the development of the next generation of intranasal drug delivery devices.

In vitro Lipolysis as a Tool for the Establishment of IVIVC for Lipid-Based Drug Delivery Systems

2019 ◽  
Vol 16 (8) ◽  
pp. 688-697
Author(s):  
Ravinder Verma ◽  
Deepak Kaushik
Keyword(s):  
Drug Delivery ◽  
Ph Value ◽  
Electron Paramagnetic Resonance Spectroscopy ◽  
Rapid Screening ◽  
Resonance Spectroscopy ◽  
Fed State ◽  
In Vitro Lipolysis ◽  
Ph Stat

: In vitro lipolysis has emerged as a powerful tool in the development of in vitro in vivo correlation for Lipid-based Drug Delivery System (LbDDS). In vitro lipolysis possesses the ability to mimic the assimilation of LbDDS in the human biological system. The digestion medium for in vitro lipolysis commonly contains an aqueous buffer media, bile salts, phospholipids and sodium chloride. The concentrations of these compounds are defined by the physiological conditions prevailing in the fasted or fed state. The pH of the medium is monitored by a pH-sensitive electrode connected to a computercontrolled pH-stat device capable of maintaining a predefined pH value via titration with sodium hydroxide. Copenhagen, Monash and Jerusalem are used as different models for in vitro lipolysis studies. The most common approach used in evaluating the kinetics of lipolysis of emulsion-based encapsulation systems is the pH-stat titration technique. This is widely used in both the nutritional and the pharmacological research fields as a rapid screening tool. Analytical tools for the assessment of in vitro lipolysis include HPLC, GC, HPTLC, SEM, Cryo TEM, Electron paramagnetic resonance spectroscopy, Raman spectroscopy and Nanoparticle Tracking Analysis (NTA) for the characterization of the lipids and colloidal phases after digestion of lipids. Various researches have been carried out for the establishment of IVIVC by using in vitro lipolysis models. The current publication also presents an updated review of various researches in the field of in vitro lipolysis.

Novel Phospholipid-Based Labrasol Nanomicelles Loaded Flavonoids for Oral Delivery with Enhanced Penetration and Anti-Brain Tumor Efficiency

2020 ◽  
Vol 17 (3) ◽  
pp. 229-245
Author(s):  
Gang Wang ◽  
Junjie Wang ◽  
Rui Guan
Keyword(s):  
Drug Delivery ◽  
Brain Tumor ◽  
Oral Delivery ◽  
Safe Delivery ◽  
Drug Delivery Vehicles ◽  
Therapeutic Benefits ◽  
Delivery Vehicles ◽  
The Brain

Background: Owing to the rich anticancer properties of flavonoids, there is a need for their incorporation into drug delivery vehicles like nanomicelles for safe delivery of the drug into the brain tumor microenvironment. Objective: This study, therefore, aimed to prepare the phospholipid-based Labrasol/Pluronic F68 modified nano micelles loaded with flavonoids (Nano-flavonoids) for the delivery of the drug to the target brain tumor. Methods: Myricetin, quercetin and fisetin were selected as the initial drugs to evaluate the biodistribution and acute toxicity of the drug delivery vehicles in rats with implanted C6 glioma tumors after oral administration, while the uptake, retention, release in human intestinal Caco-2 cells and the effect on the brain endothelial barrier were investigated in Human Brain Microvascular Endothelial Cells (HBMECs). Results: The results demonstrated that nano-flavonoids loaded with myricetin showed more evenly distributed targeting tissues and enhanced anti-tumor efficiency in vivo without significant cytotoxicity to Caco-2 cells and alteration in the Trans Epithelial Electric Resistance (TEER). There was no pathological evidence of renal, hepatic or other organs dysfunction after the administration of nanoflavonoids, which showed no significant influence on cytotoxicity to Caco-2 cells. Conclusion: In conclusion, Labrasol/F68-NMs loaded with MYR and quercetin could enhance antiglioma effect in vitro and in vivo, which may be better tools for medical therapy, while the pharmacokinetics and pharmacodynamics of nano-flavonoids may ensure optimal therapeutic benefits.

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